POS0133 TRADITIONAL LABORATORY PARAMETERS AND NEW BIOMARKERS IN MACROPHAGE ACTIVATION SYNDROME (MAS) AND SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (sHLH)
Authors: A. De Matteis, D. Pires Marafon, I. Caiello, M. Pardeo, G. Marucci, E. Sacco, F. Minoia, F. Licciardi, A. Minaici, I. Maccora, M. C. Maggio, G. Prencipe, F. De Benedetti, C. Bracaglia
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Macrophage Activation Syndrome (MAS) and Secondary Hemophagocytic Lymphohistiocytosis (sHLH) are hyperinflammatory conditions, in which IFNγ plays a pivotal role. Prompt recognition and early treatment are essential to improve the outcome and the mortality rate. <h3>Objectives</h3> This is a retrospective multicenter study. We correlated traditional laboratory parameters of hyperinflammation with IL-18 and IFNγ related biomarkers. We have also evaluated the diagnostic and prognostic role of IL-18, CXCL9, CXCL10 and neopterin in patients with MAS and sHLH. <h3>Methods</h3> One hundred-six patients from 6 Italian centers were enrolled: 41 with sHLH, 41 with MAS in the context of sJIA, and 24 with sJIA without MAS. The samples were collected at three different time points: active disease (T0), 7-10 days from starting therapy (T1) and in clinical inactive disease on medication (from 1 to 3 months from onset) (T2). Serum levels of IL-18 and of the IFN-γ related biomarkers (CXCL9, CXCL10, Neopterin) were measured by ELISA. <h3>Results</h3> A total of 378 samples were collected. Laboratory features at T0 are detailed in table 1. Using the 2016 classification criteria for MAS, we can confirm that platelet count is a specific parameter, only 2 patients with sJIA had a value &lt;181x10<sup>9</sup>/liter. Instead ferritin is a sensitive parameter, 94.4% of patients with MAS had ferritin &gt;684 mg/ml. Lactate dehydrogenase (LDH) values were statistically higher in MAS and sHLH compared to sJIA. ROC curve of LDH values in MAS showed a statistically significant area under the curve (AUC= 78.2%, p-value &lt;0.0001). A cut-off of 683 U/L had a sensitivity of 73.6% and a specificity of 70.3%. IL-18, CXCL9, CXCL10 and neopterin levels in T0 were significantly higher in MAS and sHLH compared to sJIA. In MAS, IL-18 levels were significantly higher compared to sHLH (p&lt;0.0001). The ROC curves performed for each biomarker showed a statistically significant AUCs (p&lt;0.01), except for IL-18 in sHLH. We have identified a cut off value for each biomarker in MAS (CXCL9 900 pg/ml, CXCL10 260 pg/ml, neopterin 5.0 ng/ml, IL-18 82996 pg/ml) and sHLH (CXCL9 2145 pg/ml, CXCL10 270 pg/ml, neopterin 7.1 ng/ml). In T0 neopterin correlates significantly with IL-18, CXCL9 and CXCL10 in MAS group but not in sHLH. We found also strong correlation between CXCL9 and CXCL10 only in MAS group. <h3>Conclusion</h3> Platelet count and ferritin have high specificity and sensitivity, respectively, to diagnose MAS in the context of sJIA. Even if LDH is not included in 2016 classification criteria for MAS in sJIA, we have found that this parameter could help to discriminate MAS in sJIA, in addition to the others. Our results confirm that IL-18 and the IFN-γ related biomarkers are significantly higher in patients with MAS and sHLH and might be useful to diagnose MAS/sHLH. IL-18 could help to distinguish sHLH from MAS and MAS from active sJIA. <h3>References</h3> [1]Henter JI, et al. Pediatr Blood Cancer. 2007 [2]Ravelli A, et al Annals of the Rheumatic Diseases 2016 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Arianna De Matteis: None declared, Denise Pires Marafon: None declared, Ivan Caiello: None declared, Manuela Pardeo: None declared, Giulia Marucci: None declared, Emanuela Sacco: None declared, Francesca Minoia: None declared, Francesco Licciardi: None declared, Angela Minaici: None declared, Ilaria Maccora: None declared, Maria Cristina Maggio: None declared, Giusi Prencipe: None declared, Fabrizio De Benedetti Consultant of: Abbvie, SOBI, Novimmune, Novartis, Roche, Pfizer, Claudia Bracaglia Consultant of: Novartis, SOBI.